The treatment of pain conditions is of great importance in medicine. There is currently a worldwide need for additional pain therapy. “Pain” is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (IASP, Classification of chronic pain, 2.sup.nd Edition, IASP Press (2002), 210). Physiological and psychological factors affect the perception of pain. Some of the relevant pain subtypes are nociceptive pain, inflammatory pain, neuropathic pain, allodynia, hyperalgesia, and peripheral neuropathy.
Postsurgical pain (interchangeably termed, post-incisional pain), or pain that occurs after surgery or traumatic injury, is serious and often intractable. Pain is usually localized within the vicinity of the surgical site. Post-surgical pain can have two clinically important aspects, namely resting pain, or pain that occurs when the patient is not moving, and mechanical pain which is exacerbated by movement (coughing/sneezing, getting out of bed, physiotherapy, etc.). Drugs that are used to treat this pain often have a variety of side effects that delay recovery, prolong hospitalization and can have debilitating complications.
The major classes of pharmaceutical drugs used to treat various forms of pain are opioid analgesics, local anesthetics, non-steroidal anti-inflammatory drugs (NSAID), anti-depressants, and cannabinoids. Local anesthetics (e.g. channel blockers) are administered non-systemically during surgery while the other four classes of drugs, the opioid analgesics, NSAIDs, anti-depressants, and cannabinoids, are typically administered systemically. However, all the major classes of drugs for the treatment of pain are associated with risks of drug tolerance, dependence, or abuse. Analgesic tolerance often leads to hyperalgesia, requiring higher and higher doses of medication. Based on a 2011 report, prescription drugs for pain, or painkillers, kill twice as many people as cocaine and five times as many people as heroin (Harvard Mental Health Letter, 27:4-5, 2011). A need remains for other agents that can be used to treat pain.